(i) Field of the Invention
This invention relates generally to new monoclonal antibodies and their preparation and use, as well as to a new hybridoma for the harvesting of the monoclonal antibodies and its method of production.
(ii) Description of the Prior Art
Antibodies are protein molecules found in vertebrates and are involved in the defense of the organism against foreign invasion. Antibodies are unique in that they bind with exquisite specificity to the molecule they were generated against. The mammalian immune system has the capacity to generate antibodies against virtually any organic molecule. Monoclonal antibody technology permits the identification and indefinite growth of cells that produce a single species of antibody which binds to a molecule of choice. This enables the production of virtually an unlimited amount of specific antibody directed against virtually any molecule of biological interest.
Monoclonal antibodies having a definite antigen binding specificity may be produced employing the hybridoma technique developed by Kohler and Milstein (Nature 256, 495-497, 1975), or modifications thereof.
While the concept of the technique of producing monoclonal antibodies from hybridomas is understood, there are many difficulties met and variations required for each specific case.
Indeed, there is no assurance, prior to attempting the preparation of a particular hybridoma, that the hybridoma will be obtained, that the hybridoma will produce an antibody, or that any antibody so produced will have the desired specificity.
The functional integrity of the mammalian reproductive system is dependent on the correct levels and interplay of the various sex hormones. Key among these hormones is a small polypeptide produced in the hypothalamus of the brain. This polypeptide, termed GnRH, (Gonadotropic Releasing Hormone) also known as LHRH (Luteinizing Hormone Releasing Hormone) is released into the blood and is active on the pituitary gland. (Schally, A. V., A. Arimura, A. J. Kastin (1973). "Hypothalamic regulating hormones." Science 179:341-350.) Here it effects the release of two protein sex hormones, the gonadotropins Luteinizing Hormone (LH) and the Follice Stimulating Hormone (FSH). These two hormones then act in concert on the gonads, namely the ovaries in females and the testes in males, to produce normal development of egg cells or sperm. In addition LH induces ovulation in the female. Thus it is seen that GnRH is required in general for the maintenance of reproductive functions in both male and female, and also on an acute basis for cyclicity in females.
Immunological neutralization of GnRH is an effective way to block the normal patterns of GnRH release and thus to effect reproductive functions. This has been shown in laboratory animals and domestic species after active and passive immunization against GnRH. (Arimura, A., C. Debeljuk, A. V. Schally (1974). "Blockade of the Preovulatory Surge of LH and FSH and of Ovulation by anti-LH-RH Serum in Rats." Endo 95:323-325; McCormack, J. T., T. M. Plant, D. L. Hess, E. Knobil (1977). "The Effect of Luteinizing Hormone Releasing Hormone (LHRH) Antiserum Administration of Gonadotropin Secretion in the Rhesus Monkey." Endo 100:663-667; Jeffcoate, I. A., J. P. Foster, D. B. Crighton (1978). "Effect of Active Immunization of Ewes Against Synthetic Luteinizing Hormone Releasing Hormone." Therio 10:323-325; and Schanbacher, B. D. (1982). "Responses of Ram Lambs to Active Immunization Against Testosterone and Luteinizing Hormone-Releasing Hormone." Am. J. Physio. 242(3), E201-5.)